1. Field of the Invention
The present invention relates to polymers, and particularly to nanocarrier-forming poly(ε-caprolactone)-poly ethoxylated fatty acid block copolymers.
2. Description of the Related Art
Ethoxylated fatty acids that are sold under the trademark Myrj™ are non-ionic surfactants widely used with various drug delivery systems. The presence of PEG (poly ethylene glycol) in the molecule extends the circulation time of the drug in plasma, while fatty acid enhances the solubility of the fat-soluble drug. Several derivatives of these ethoxylated fatty acids with different PEG chain lengths have been studied. Depending on the length of PEG used, the ethoxylated fatty acid products have hydrophilic-lipophilic balance (HLB) values in the range of 11-18.8 and critical micelle concentrations (CMC) in the micro molar range.
The US FDA has approved the ethoxylated fatty acids sold under the trademark Myrj™ as safe pharmaceutical excipients used in drug formulation and food additives. In recent years, the ethoxylated fatty acids have been extensively used in the pharmaceutical industry. Several of these ethoxylated fatty acid products have been used as absorption enhancers, emulsifiers, solubilizers, permeation enhancers and stabilizers. Some derivatives of these ethoxylated fatty acids have also been used as inhibitors of P-gp (p-glycoprotein) to increase the oral bioavailability of P-gp substrates.
Poly(ε-Caprolactone) (PCL) is a biodegradable and biocompatible polyester that has been extensively studied for controlled drug delivery and tissue engineering applications. It has the advantage of being compatible with a wide range of drugs, which allows homogenous drug distribution in the polymer matrix. Moreover, PCL exhibit a long degradation time leading to sustained drug release that could last for months. PCL has flexible mechanical properties that are suitable for medical applications including drug delivery. Compared to other core-forming blocks in the poly(ester) category, such as PLGA (poly(lactic-co-glycolic acid)) and PLA (poly D-lactic acid), PCL is more hydrophobic, which makes it more compatible with hydrophobic drugs. The hydrophobicity of PCL has pushed the CMC of PEG-b-PCL to extremely low concentration in 100 nM range. PCL-based polymeric micelles have been successfully used to deliver a variety of lipophilic drugs including P-gp inhibitors such as Cyclosporine A and valspodar and some of the chemotherapeutic agents such as doxorubicin and paclitaxel. Thus, PCL is an important synthetic biomedical material with controlled biodegradability, which has already been approved by US FDA and European Medicines Agency (EMA) for clinical use as implants/drug delivery system.
Thus, biodegradable block copolymers for use in drug delivery systems are desired.